INFLUENCE OF OPENER OF KATPCHANNELS OF FLOCALIN ON OXIDATIVE METABOLISM, THE ACTIVITY OF NOSYNTHASES AND BLOOD OXYGENATION
R.B. Strutynskyi, Yu.P. Korkach, V.R. Strutynskyi, R.A. Rovenets
O.O. Bogomoletz Institute of Physiology National Academy of Science of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz64.03.009
Abstract
In the experiments on the anesthetized dogs, the effects of
ATP-sensitive potassium (KATP) channels activation by flocalin
on the activity of endothelial and inducible NO-synthases
(iNOS), heme oxygenase reaction, blood oxygenation and
free radical processes were studied. Changes in biochemical
parameters in arterial blood were determined after 20 and 60
minutes after intravenous administration of flocalin in doses
of 0.1, 0.5, 1.0 and 1.5 mg/kg. It is shown that the opening of
KATP-channels dose-dependent increases the level of protective
constitutive synthesis of nitric oxide and, conversely, inhibits
inducible synthesis (at 2.8 and 2.1 times at a dose of flocalin
1.5 mg/kg, respectively). The activation of the above channels
is a powerful antihypoxic mechanism – greatly enhances the
oxygenation of arterial blood and the content of nitrite anion
(at 3.7 and 3.0 times at a dose of 1,0 mg/kg, respectively).
Flocalin significantly reduced the content of the products of the
heme oxygenase reaction - iron and bilirubin (with a maximum
effect of 2.9 and 1.9 times respectively), which may indicate
inhibition of the activity of the enzyme heme oxygenase.
Аctivation of KATP-channels dose-dependently suppresses free
radical processes (decrease in the generation of superoxide
anion and hydrogen peroxide (5.3 and 7.2 times at a dose of
1.5 mg/kg, respectively) and exhibits antioxidant properties
(decrease in the content of diene conjugates by 6.3 times at
a dose of 1.5 mg/kg), inhibits the formation of peroxynitrite
by reducing the generation of superoxide anion (uric acid
content) and inducible nitric oxide. Thus, the activation of
KATP-channels by flocalin increases the constitutive synthesis
of NO and, conversely, reduces the inducible synthesis of NO,
greatly enhances the oxygenation of arterial blood, suppresses
free radical processes and the activity of heme oxygenase.
Keywords:
ATP-sensitive potassium channels; flocalin; NOsynthases; free radicals; heme oxygenase
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